Interferon, in particular interferon α-2a, is a pharmaceutically active protein which has antiviral and antiproliferative activity. For example interferon is used to treat hairy cell leukemia and Kaposi's sarcoma, and is active against hepatitis. In order to improve stability and solubility, and reduce immunogenicity, pharmaceutically active proteins such as interferon may be conjugated to the polymer polyethylene glycol (PEG).
The bioavailability of protein therapeutics are often limited due to their short plasma half-life, thus preventing them from attaining their maximum clinical potency. In recent years, PEG conjugated biomolecules have been shown to possess clinically useful properties (Inada, Delgado, Katre I). Among these are better physical and thermal stability, protection against susceptibility to enzymatic degradation, increased solubility, longer in vivo circulating half-life and decreased clearance, enhancing potency. It has been reported that branched PEG conjugates exhibit increased pH and thermal stability and greater stability towards proteolytic digestion than linear PEG conjugates. (Monfardini). Other properties of PEG proteins are reduced immunogenicity and antigenicity, as well as reduced toxicity. Another effect of PEGylation of certain proteins may be reduced in vitro activity accompanied by enhanced in vivo activity. This has been observed in G-CSF (Satake-Ishikawa), IL-2 (Katre II), TNF-α (Tsutsumi), IL-6 (Inoue) CD4-IgG (Chamow), among others.